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Absence of correlation between radiation-induced CD8 T-lymphocyte apoptosis and sequelae in patients with prostate cancer accidentally overexposed to radiation.

ABSTRACT: 454 patients with prostate adenocarcinoma were accidentally overexposed to radiation in Epinal hospital, France, between August 1999 and January 2007. We aimed toevaluate whether radiation-induced CD4 or CD8 T-lymphocyte apoptosis (RILA) correlates with the severity of radiation toxicity.Between 2007 and 2013, all patients who received more than 108% of the prescribed radiation dose, after correction of the treatment plan, were convened, and blood was sampled at 6-months follow-up. Maximal Digestive toxicity (MDT) and maximal urinary toxicity (MUT) were graded using the Common Terminology Criteria for Adverse Events (NCI-CTCAE) v3.0 scale. RILA was assessed using flow cytometry.245 patients were included in our study. After a median follow-up of 4.8 years, the MDT and MUT reached grade 3-4 in 37 patients and 56 patients, respectively. Patients with prostatectomy exhibited a statistically higher grade of MUT compared with those treated with definitive radiotherapy (p=0.03). The median RILA values were 11.8% and 15.3% for CD4 and CD8 T-lymphocytes, respectively. We found no significant correlation between CD4 or CD8 RILA and either MDT or MUT.RILA does not correlate with the inter-individual variation in MDT or MUT in the largest cohort of patients overexposed to radiation. The magnitude of the overdosage probably overrides biological predictors of toxicity, including individual radiosensitivity.

SUBMITTER: Vogin G

PROVIDER: S-EPMC6135683 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Absence of correlation between radiation-induced CD8 T-lymphocyte apoptosis and sequelae in patients with prostate cancer accidentally overexposed to radiation.

Vogin Guillaume G Merlin Jean-Louis JL Rousseau Alexandra A Peiffert Didier D Harlé Alexandre A Husson Marie M Hajj Labib El LE Levitchi Mihai M Simon Tabassome T Simon Jean-Marc JM

Oncotarget 20180824 66

<h4>Purpose</h4>454 patients with prostate adenocarcinoma were accidentally overexposed to radiation in Epinal hospital, France, between August 1999 and January 2007. We aimed toevaluate whether radiation-induced CD4 or CD8 T-lymphocyte apoptosis (RILA) correlates with the severity of radiation toxicity.<h4>Methods</h4>Between 2007 and 2013, all patients who received more than 108% of the prescribed radiation dose, after correction of the treatment plan, were convened, and blood was sampled at 6 ...[more]

PMID: 30220974

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Project description:Monocentric cohorts suggested that radiation-induced CD8 T-lymphocyte apoptosis (RILA) can predict late toxicity after curative intent radiotherapy (RT). We assessed the role of RILA as a predictor of breast fibrosis (bf +) after adjuvant breast RT in a prospective multicenter trial.A total of 502 breast-cancer patients (pts) treated by conservative surgery and adjuvant RT were recruited at ten centers. RILA was assessed before RT by flow cytometry. Impact of RILA on bf + (primary endpoint) or relapse was assessed using a competing risk method. Receiver-operator characteristic (ROC) curve analyses were also performed in intention to treat. This study is registered with ClinicalTrials.gov, number NCT00893035 and final analyses are presented here.Four hundred and fifty-six pts (90.8%) were included in the final analysis. One hundred and eight pts (23.7%) received whole breast and node irradiation. A boost dose of 10-16 Gy was delivered in 449 pts (98.5%). Adjuvant hormonotherapy was administered to 349 pts (76.5%). With a median follow-up of 38.6 months, grade ? 2 bf + was observed in 64 pts (14%). A decreased incidence of grade ? 2 bf + was observed for increasing values of RILA (p = 0.012). No grade 3 bf + was observed for patients with RILA ? 12%. The area under the ROC curve was 0.62. For cut-off values of RILA ? 20% and < 12%, sensitivity and specificity were 80% and 34%, 56% and 67%, respectively. Negative predictive value for grade ? 2 bf + was equal to 91% for RILA ? 20% and positive predictive value was equal to 22% for RILA < 12% where the overall prevalence of grade ? 2 bf + was estimated at 14%. A significant decrease in the risk of grade ? 2 bf + was found if patients had no adjuvant hormonotherapy (sHR = 0.31, p = 0.007) and presented a RILA ? 12% (sHR = 0.45, p = 0.002).RILA significantly predicts the risk of breast fibrosis. This study validates the use of RILA as a rapid screening test before RT delivery and will change definitely our daily clinical practice in radiation oncology.The French National Cancer Institute (INCa) through the "Program Hospitalier de Recherche Clinique (PHRC)".

Project description:BackgroundColorectal cancer is one of the most common cancers worldwide. Psychological morbidity has an important impact on quality of life and major clinical outcomes. Several data have shown that the immune system may be a key player on the relation between psychological features and cancer outcomes. Natural Killer (NK) cells have been shown to be influenced by psychological factors. The aim of this investigation was to assess the impact of anxiety, depression, and anger state, trait, and expression on the immune response, particularly, their effect on NK cells and CD8+ T cells in surgical colorectal cancer patients.MethodsWe studied 54 surgical colorectal cancer patients and assessed patients pre-surgically, post-surgically, and 12 months after surgery (follow-up). We applied the Hospital Anxiety and Depression Scale and the State-Trait Anger Expression Inventory and measured peripheral T cells, CD8+ T cells, and NK cells. We did a cross-sectional analysis as well as a longitudinal assessment of the variables during the follow-up period.ResultsPre-surgical assessment: Trait anger, angry reaction, and anger-out had a significant negative correlation with NK cells. The lymphocytes values were unaffected by the presence of clinical anxiety or depression. Post-surgical assessment: Patients without clinical anxiety had higher levels of T cells. Angry reaction was negatively correlated with NK cells. Lymphocytes values were unaffected by the presence of clinical depression. Follow-up assessment: Patients without clinical depression had higher T cell counts. Trait anger and angry reaction were negatively correlated with the levels of NK cells. The lymphocytes values were unaffected by the presence of clinical anxiety. Longitudinal assessment: Angry-temperament, anger expression, and anger-in reduced significantly from the first to the second assessment. Anxiety, state anger, and trait anger significantly diminished from the pre-surgical to the follow-up assessment. Depression levels did not alter during the follow-up period. The lymphocyte count, and particularly T cells and CD8+ T cells, was significantly higher in the follow-up when compared with the pre-surgical assessment.ConclusionOur study suggests the existence of a relation between psychological response and immune response in colorectal cancer patients. We identified the importance of emotional regulation as a potential modulator for NK cell counts. Higher values of propensity to experience anger states and express them outwards seem to be associated with lower NK cell counts.

Project description:BACKGROUND: Members of the PDGF family have been suggested as potential biomarkers for papillary thyroid carcinomas (PTC). However, it is known that both expression and stimulatory effect of PDGF ligands can be affected by inflammatory cytokines. We have performed a microarray study in a collection of PTCs, of which about half the biopsies contained tumour-infiltrating lymphocytes or thyroiditis. To investigate the expression level of PDGF ligands and receptors in PTC we measured the relative mRNA expression of all members of the PDGF family by qRT-PCR in 10 classical PTC, eight clinically aggressive PTC, and five non-neoplastic thyroid specimens, and integrated qRT-PCR data with microarray data to enable us to link PDGF-associated gene expression profiles into networks based on recognized interactions. Finally, we investigated potential influence on PDGF mRNA levels by the presence of tumour-infiltrating lymphocytes. METHODS: qRT-PCR was performed on PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA PDGFRB and a selection of lymphocyte specific mRNA transcripts. Semiquantitative assessment of tumour-infiltrating lymphocytes was performed on the adjacent part of the biopsy used for RNA extraction for all biopsies, while direct quantitation by qRT-PCR of lymphocyte-specific mRNA transcripts were performed on RNA also subjected to expression analysis. Relative expression values of PDGF family members were combined with a cDNA microarray dataset and analyzed based on clinical findings and PDGF expression patterns. Ingenuity Pathway Analysis (IPA) was used to elucidate potential molecular interactions and networks. RESULTS: PDGF family members were differentially regulated at the mRNA level in PTC as compared to normal thyroid specimens. Expression of PDGFA (p = 0.003), PDGFB (p = 0.01) and PDGFC (p = 0.006) were significantly up-regulated in PTCs compared to non-neoplastic thyroid tissue. In addition, expression of PDGFC was significantly up-regulated in classical PTCs as compared to clinically aggressive PTCs (p = 0.006), and PDGFRB were significantly up-regulated in clinically aggressive PTCs (p = 0.01) as compared to non-neoplastic tissue. Semiquantitative assessment of lymphocytes correlated well with quantitation of lymphocyte-specific gene expression. Further more, by combining TaqMan and microarray data we found a strong inverse correlation between PDGFC expression and the expression of lymphocyte specific mRNAs. CONCLUSION: At the mRNA level, several members of the PDGF family are differentially expressed in PTCs as compared to normal thyroid tissue. Of these, only the PDGFC mRNA expression level initially seemed to distinguish classical PTCs from the more aggressive PTCs. However, further investigation showed that PDGFC expression level correlated inversely to the expression of several lymphocyte specific genes, and to the presence of lymphocytes in the biopsies. Thus, we find that PDGFC mRNA expression were down-regulated in biopsies containing infiltrated lymphocytes or thyroiditis. No other PDGF family member could be linked to lymphocyte specific gene expression in our collection of PTCs biopsies.

Dataset Information

Absence of correlation between radiation-induced CD8 T-lymphocyte apoptosis and sequelae in patients with prostate cancer accidentally overexposed to radiation.

Publications

Absence of correlation between radiation-induced CD8 T-lymphocyte apoptosis and sequelae in patients with prostate cancer accidentally overexposed to radiation.

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